A Phase II Trial of Upfront Radiotherapy Plus Almonertinib for Epidermal Growth Factor Receptor(EGFR)-Mutant Non-small-cell Lung Cancer(NSCLC) Patients With Brain Metastases

November 19, 2020 updated by: First People's Hospital of Hangzhou

Upfront Radiotherapy Combined With Almonertinib for Brain Metastasis in Non-small Cell Lung Cancer With EGFR Mutation: A Prospective Single-arm Phase II Trial

Almonertinib is a three-generation epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI), which has shown competitive potential in the second-line treatment against first-generation TKIs. This study intends to assess the efficacy and safety of stereotactic radiosurgery with sequential almonertinib in treatment-naive EGFR-mutant NSCLC patients with brain metastases.

Study Overview

Status

Not yet recruiting

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

47

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Zhejiang
      • Hangzhou, Zhejiang, China, 310002
        • Hangzhou Cancer Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologically or pathologically confirmed non-small-cell lung cancer (adenocarcinoma).
  2. The presence of radiographically definite brain metastases and intracranial foci measurable according to the RANO-BM criteria.
  3. The number of brain metastases ≤ 10, the volume of individual metastases ≤ 15 cc, the diameter of individual metastases ≤ 30 mm, the diameter of metastases in the brainstem ≤ 5 mm, distance of the foci from the optic nerve, or optic cross > 5 mm.
  4. EGFR-sensitive mutations (include 19del or L858R mutation or coexist with other types of EGFR mutation).
  5. Comply with the indications and drug instructions for first-line treatment with a third-generation EGFR-TKI.
  6. Have not received systemic antineoplastic therapy, excluding neoadjuvant, adjuvant, or synchronous chemotherapy more than 6 months prior to enrollment.
  7. Asymptomatic or mildly symptomatic brain metastases (e.g., headache, nausea, or seizures for which dexamethasone/analgesic/antiepileptic medication is effective and sustained at a steady dose for 3 days or more).
  8. Age ≥ 18 years.
  9. Eastern Cooperative Oncology Group (ECOG) performance status(PS) score ≤ 2.
  10. Survival is expected to be ≥ 6 months.
  11. Women must use contraception after surgical sterilization, after sterilization, or during and for three months after treatment.
  12. With informed consent signed.

Exclusion Criteria:

  1. Previous treatment with almonertinib or other EGFR-TKI.
  2. Patients with symptomatic brain metastases resulting in neurological deficits (not including headaches, nausea, or controlled seizures).
  3. Multiple sclerosis.
  4. Pacemakers implanted in the body or metals that cannot be examined by MRI.
  5. Allergy to magnetic resonance contrast agents.
  6. Brain metastases requiring surgical decompression.
  7. Meningeal metastases.
  8. Previous radiotherapy or surgery for brain metastases.
  9. Contraindications to radiotherapy for uncontrolled systemic lupus erythematosus, scleroderma, or other connective tissue diseases.
  10. Other malignant neoplasms (except non-melanoma skin cancer and cervical cancer) within five years.
  11. Any medical or non-medical reason that prevents the patient from continuing to participate in research.
  12. It is expected that the patient will not be able to comply with the procedures, restrictions, and requirements of the study and the investigator determines that the patient is unfit to participate in the study.
  13. Received studying drugs within 5 half-lives or 3 months, whichever is greater.
  14. Currently receiving drugs or herbal supplements known to be potent inducers of Cytochrome P450 3A4(CYP3A4) or unable to be discontinued prior to receiving the first dose of study treatment) (at least 3 weeks prior).
  15. The patient is taking any drug known to prolong the QT interval and cannot be discontinued until treatment with amitriptyline.
  16. Pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Stereotactic radiosurgery with Almonertinib
110mg Almonertinib is administered orally daily since the first day after stereotactic radiosurgery treatment (total dose 30 Gy, 5 fractions, day1, 3, 5, calibrated by CBCT before each treatment). For patients who are assessed as oligometastasis three months after Almonertinib treatment, SBRT is recommended for oligometastatic lesions
110mg Almonertinib is administered orally daily since the first day after stereotactic radiosurgery treatment (total dose 30 Gy, 5 fractions, day1, 3, 5, calibrated by CBCT before each treatment). For patients who are assessed as oligometastasis three months after Almonertinib treatment, SBRT is recommended for oligometastatic lesions (The number of lesions received SBRT and radiation dose are not standardized).
Other Names:
  • HS-10296

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central nerve system duration of response(CNS DOR)
Time Frame: 1 year
Central nerve system duration of response assessed by RANO-BM criteria
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial prgression-free survival(PFS)
Time Frame: 1 year
Intracranial progression free survival assessed by Response Assessment in Neuro-Oncology Brain Metastases(RANO-BM) criteria
1 year
Intracranial response rate(RR)
Time Frame: 1 year
Intracranial response rate assessed by RANO-BM criteria
1 year
Extracranial RR
Time Frame: 1 year
Extracranial response rate assessed by Response Evaluation Criteria in Solid Tumors(RECIST) criteria
1 year
overall survival (OS)
Time Frame: 1 year
overall survival
1 year
Neurocognitive function assessed by mini-mental state examination(MMSE) questionnaire score
Time Frame: 1 year
Neurocognitive function assessed by mini-mental state examination(MMSE) questionnaire score
1 year
quality of life(QoL) assessed by EORTC QLQ-C30
Time Frame: 1 year
Quality of Life assessed by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30(EORTC QLQ-C30)
1 year
quality of life(QoL) assessed by EORTC QLQ-BN20
Time Frame: 1 year
Quality of Life assessed by The European Organization for Reasearch and Treatment of Cancer Quality of Life Questionnaire Brain Cancer 20(BN20)
1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial RR accessed by volumetric criteria
Time Frame: 1 year
Intracranial response rate accessed by volumetric criteria
1 year
intracranial progression rate assessed by brain MRI at 1year
Time Frame: 1 year
intracranial progression rate assessed by brain MRI at 1year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

November 30, 2020

Primary Completion (Anticipated)

November 30, 2022

Study Completion (Anticipated)

November 30, 2023

Study Registration Dates

First Submitted

November 15, 2020

First Submitted That Met QC Criteria

November 19, 2020

First Posted (Actual)

November 25, 2020

Study Record Updates

Last Update Posted (Actual)

November 25, 2020

Last Update Submitted That Met QC Criteria

November 19, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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